首页> 外文期刊>American Journal of Physiology >Adriamycin impairs the contraction of mesangial cells through the inhibition of protein kinase C and intracellular calcium.
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Adriamycin impairs the contraction of mesangial cells through the inhibition of protein kinase C and intracellular calcium.

机译:阿霉素通过抑制蛋白激酶C和细胞内钙而损害系膜细胞的收缩。

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摘要

The effects of adriamycin on the contractile function of cultured mesangial cells were measured by the changes in planar surface area in response to treatment with agonists. Incubation of mesangial cells with adriamycin (0.2 microg/ml) for 24 h significantly decreased the contractile responses to the calcium channel activator BAY K 8644 (1 microM) and to the PKC activator PMA (1 microM). Intracellular calcium concentration ([Ca(2+)](i)), measured by changes in fura 2 levels in response to ATP (0.1 mM), was significantly inhibited in adriamycin-treated mesangial cells compared with control cells. In the absence of extracellular calcium, treatment with ionomycin (0.1 mM) or thapsigargin (10 microM) resulted in a significantly smaller increase in [Ca(2+)](i) in adriamycin-treated mesangial cells compared with control, suggesting an important role of the endoplasmic reticulum in the effects of adriamycin. Using PKC-specific antibodies, adriamycin significantly decreased the cytosolic and membranous fractions of PKC-alpha in mesangial cells to 75 +/- 6 and 70 +/- 12% of control, respectively. The PKC activity of mesangial cells was also significantly inhibited after incubation with adriamycin for 24 h. In conclusion, adriamycin induces hypocontractility of mesangial cells, which may mediate this effect by inhibiting PKC-alpha and [Ca(2+)](i).
机译:阿霉素对培养的系膜细胞的收缩功能的影响通过响应于激动剂处理的平面表面积的变化来测量。肾小球系膜细胞与阿霉素(0.2微克/毫升)孵育24小时显着降低了对钙通道激活剂BAY K 8644(1 microM)和对PKC激活剂PMA(1 microM)的收缩反应。与对照组相比,在阿霉素处理的系膜细胞中,胞内钙浓度([Ca(2 +)](i))通过响应ATP(0.1 mM)的呋喃2水平变化而显着抑制。在缺乏细胞外钙的情况下,与对照组相比,用离子霉素(0.1 mM)或毒胡萝卜素(10 microM)进行治疗后,阿霉素处理的系膜细胞中[Ca(2 +)](i)的增加显着减小。内质网在阿霉素作用中的作用使用PKC特异性抗体,阿霉素可将肾小球膜细胞中PKC-α的胞质和膜部分分别降低至对照组的75 +/- 6和70 +/- 12%。与阿霉素孵育24小时后,系膜细胞的PKC活性也被显着抑制。总之,阿霉素诱导肾小球系膜细胞收缩性降低,这可能通过抑制PKC-α和[Ca(2 +)](i)介导此作用。

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